PubMed Health⌕ Search

SEARCH · PubMed Health

Results for “Skeletal muscle dysfunction”

Explore indexed PubMed citations for clinical trials, systematic reviews and public health research. Read source abstracts and follow each citation to its original PubMed record.

Quote a phrase for an exact phrase match. Source license links do not imply unrestricted reuse.

At least 955 records · Page 53Linked to original sources
PubMed2004

The slow skeletal muscle troponin T gene is expressed in developing and diseased human heart.

Cardiac muscle development is characterised by the activation of contractile protein genes and subsequent modulation of expression resulting, ultimately, in the formation of a mature four-chambered organ. Myocardial gene expression is also altered in the adult in response to pathological stimuli and this is thought to contribute to the altered contractile characteristics of the diseased heart. We have examined the expression of the slow skeletal troponin T (TnT) gene in the human heart during development and in disease using whole mount in situ hybridisation and real-time quantitative (TaqMan) polymerase chain reaction (PCR). Slow skeletal TnT mRNA shows transitory and regional expression in the early foetal heart, which occurs at different times in atria and ventricles. In ventricular myocardium, expression is seen in the outer epicardial layer at a time when the coronary circulation is being established. Expression was detected at low levels in the adult human heart and was significantly increased in end-stage heart failure. Similarly, expression was readily detectable during early rat heart development and was up-regulated in pressure overload hypertrophy in adult. Together these data show for the first time that slow skeletal TnT mRNA is readily detectable during early human heart development. They further suggest that slow skeletal TnT may be responsive to myocardial stress and that elevated levels may contribute to myocardial dysfunction in adult disease.

Adult↗
PubMed2006

Proteolytic processing of OPA1 links mitochondrial dysfunction to alterations in mitochondrial morphology.

Many muscular and neurological disorders are associated with mitochondrial dysfunction and are often accompanied by changes in mitochondrial morphology. Mutations in the gene encoding OPA1, a protein required for fusion of mitochondria, are associated with hereditary autosomal dominant optic atrophy type I. Here we show that mitochondrial fragmentation correlates with processing of large isoforms of OPA1 in cybrid cells from a patient with myoclonus epilepsy and ragged-red fibers syndrome and in mouse embryonic fibroblasts harboring an error-prone mitochondrial mtDNA polymerase gamma. Furthermore, processed OPA1 was observed in heart tissue derived from heart-specific TFAM knock-out mice suffering from mitochondrial cardiomyopathy and in skeletal muscles from patients suffering from mitochondrial myopathies such as myopathy encephalopathy lactic acidosis and stroke-like episodes. Dissipation of the mitochondrial membrane potential leads to fast induction of proteolytic processing of OPA1 and concomitant fragmentation of mitochondria. Recovery of mitochondrial fusion depended on protein synthesis and was accompanied by resynthesis of large isoforms of OPA1. Fragmentation of mitochondria was prevented by overexpressing OPA1. Taken together, our data indicate that proteolytic processing of OPA1 has a key role in inducing fragmentation of energetically compromised mitochondria. We present the hypothesis that this pathway regulates mitochondrial morphology and serves as an early response to prevent fusion of dysfunctional mitochondria with the functional mitochondrial network.

Animals↗
PubMedDate not supplied

Exercise testing and training of patients with heart failure due to left ventricular systolic dysfunction.

Reducing the exercise intolerance and symptoms experienced by patients with chronic heart failure remains an important focus in their clinical care. A clear shortcoming exists; however, with respect to an appreciation that in addition to standard medical therapy, selected patients with stable heart failure also can benefit from a moderate exercise training program. Improvements in central transport, regional blood flow, and skeletal muscle histology and biochemistry all likely account for the increase in exercise capacity and delay in fatigue that these patients experience. Additionally, the autonomic imbalance that is characteristic of these patients is improved. Although the number of patients with heart failure participating in an exercise program is increasing, much work still exists relative to incorporating this treatment method into the care plans established by physicians and physician extenders.

Exercise Test↗
PubMed1997

A review of effects of hypothyroidism on vascular transport in skeletal muscle during exercise.

Hypothyroidism is a common thyroid disease characterized by exercise intolerance. Both exercise capacity and endurance are compromised in the hypothyroid state. Studies involving rats performing treadmill running have shown that blood flows during exercise to high oxidative, extensor-type muscles are lower in hypothyroid rats compared with those in euthyroid rats. Abnormal cardiac and vascular function appear to contribute to this hypoperfusion. Experiments involving isolated arterial vessel segments have demonstrated that potential for constriction is normal in vessels from hypothyroid animals; however, reduced vasodilator potential is associated with hypothyroidism. Dysfunction of both endothelium and vascular smooth muscle appear to contribute to blunted potential for vasodilation. Altered ability to generate vasodilatory substances and/or changes in responses to these vasodilators may account for vascular dysfunction. It appears that impaired vascular function interacts with other factors such as poor myocardial function and changes in energy metabolism to compromise exercise tolerance.

Animals↗
PubMed1995

Biochemical evaluations in skeletal muscles of primates with MPTP Parkinson-like syndrome.

The toxic effects of the neurotoxin MPTP (1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine) in primates can be exploited for investigating the physiopathology of Parkinson's disease which may also cause functional alterations of skeletal muscles, whose biochemical modifications have been studied very little. Some enzyme activities related to energy transduction in skeletal muscles were evaluated (gastrocnemius, soleus and biceps) from MPTP-treated monkeys. Systemically administered MPTP altered the enzyme activities related to: (i) the anaerobic glycolytic pathway (decrease in hexokinase and phosphofructokinase activities; increase in lactate dehydrogenase activity); (ii) the tricarboxylic acid cycle (decrease in malate dehydrogenase activity); (iii) the electron transfer chain (decrease in cytochrome oxidase activity related to complex IV). No alteration in mitochondrial Complex I was observed. Treatment with an ergot alkaloid derivative (dihydroergocryptine) modified some alterations in the muscle enzyme activities and reduced the rigidity and some autonomic dysfunction.

1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine↗
PubMed2004

SANDO: another presentation of mitochondrial disease.

PURPOSE: To describe a unique mitochondrial syndrome that may present with the combination of ocular manifestations, sensory symptoms, and speech dysfunction. DESIGN: Case report. METHODS: Case report and review of the literature. RESULTS: A 43-year-old man presented with a Sensory Ataxic Neuropathy, Dysarthria, and Ophthalmoparesis (SANDO). Nerve conduction studies showed a sensory ganglionopathy. Skeletal muscle biopsy revealed ragged red fibers, and polymerase chain reaction analysis of the tissue demonstrated multiple mitochondrial DNA deletions. CONCLUSION: Mitochondrial disease should be considered in cases of external ophthalmoplegia, especially if a sensory ganglionopathy and dysarthria are present.

Adult↗
PubMed1999

Dietary protein or arginine deficiency impairs constitutive and inducible nitric oxide synthesis by young rats.

Effects of dietary protein or arginine deficiency on constitutive and lipopolysaccharide (LPS)-induced nitric oxide (NO) synthesis were determined in young rats by quantifying urinary nitrate excretion. In Experiment 1, 30-d-old rats (n = 16) were divided randomly into two groups (n = 8/group) and pair-fed on the basis of body weight semipurified isocaloric diets containing 20 or 5% casein. In Experiment 2, 30-d-old rats (n = 24) were divided randomly into three groups (n = 8) and pair-fed on the basis of body weight purified isonitrogenous and isocaloric diets (composed of amino acids) containing 0.0, 0.3 or 1.0% L-arginine. In both experiments, daily collection of urine was initiated 10 d after the start of pair-feeding. On d 17 after the pair-feeding was initiated, LPS (1 mg/kg body wt) was injected intraperitoneally into rats, and urine was collected daily for an additional 7 d. In Experiments 3 and 4, activities of constitutive and inducible NO synthases were measured in macrophages and various tissues from protein- or arginine-deficient rats (n = 6). Body weight was lower in rats fed the 5% casein diet or the 0.0 and 0.3% arginine diets than in those fed 20% casein or 1% arginine, respectively. Dietary protein or arginine deficiency decreased serum concentrations of arginine and urinary nitrate excretion before and after LPS treatment, indicating impaired constitutive and inducible NO synthesis. Protein malnutrition reduced constitutive and inducible NO synthase activities in brain, heart, jejunum, lung, skeletal muscle and spleen, and inducible NO synthase activity in macrophages. Because NO is a mediator of the immune response and is the endothelium-dependent relaxing factor, impaired NO synthesis may help explain immunodeficiency and cardiovascular dysfunction in protein- or arginine-deficient subjects.

Amino Acids↗
PubMed2005

Proton NMR spectroscopy shows lipids accumulate in skeletal muscle in response to burn trauma-induced apoptosis.

Burn trauma triggers hypermetabolism and muscle wasting via increased cellular protein degradation and apoptosis. Proton nuclear magnetic resonance (1H NMR) spectroscopy can detect mobile lipids in vivo. To examine the local effects of burn in skeletal muscle, we performed in vivo 1H NMR on mice 3 days after burn trauma; and ex vivo, high-resolution, magic angle spinning (1)H NMR on intact excised mouse muscle samples before and 1 and 3 days after burn. These samples were then analyzed for apoptotic nuclei using a terminal deoxynucleotidyl transferase-mediated dUTP nick end-labeling (TUNEL) assay. To confirm our NMR and cell biology results, we used transcriptome analysis to demonstrate that burn trauma alters the expression of genes involved in lipid metabolism and apoptosis. Our results demonstrate that burn injury results in a localized intramyocellular lipid accumulation, which in turn is accompanied by burn-induced apoptosis and mitochondrial dysfunction, as seen by the up-regulation of apoptotic genes and down-regulation of genes that encode lipid oxidation and the peroxisomal proliferator activator receptor gamma coactivator PGC-1beta. Moreover, the increased levels of bisallylic methylene fatty acyl protons (2.8 ppm) and vinyl protons (5.4 ppm), in conjunction with the TUNEL assay results, further suggest that burn trauma results in apoptosis. Together, our results provide new insight into the local physiological changes that occur in skeletal muscle after severe burn trauma.

Apoptosis↗
PubMed2005

Transient decrease of neutrophil chemotaxis following aerobic exercise.

PURPOSE: Intense exercise affects the immune system, increasing the susceptibility of athletes to viral and bacterial infections. We have previously shown a significant decrease of fMLP-neutrophil migration 24 h after aerobic exercise. In this study we aimed to look at the differential effect of different chemoattractants on neutrophil migration following aerobic exercise, to determine the recovery time, and to better understand the role of the cell skeleton behind the impaired chemotaxis. METHODS: Sixteen female volunteers aged 22-30 yr were tested before, 24, and 48 h after aerobic exercise (30 min running at 70% (.)VO(2max). The submaximal exercise test was conducted a week after the (.)VO(2max) test. We studied the membrane cell receptor response to fMLP, IL-8, and C5a, which have specific ligand-receptor pathways. Further, we studied the cytoskeletal response by investigating the cell polarization and the F-actin polymerization. RESULTS: Significant decrease of the neutrophil net chemotaxis was detected with fMLP, IL-8 and C5a, 24 h after exercise (50 +/- 5%, P = 0.0001; 48 +/- 12%, P = 0.0015; and 32 +/- 11%, P = 0.011, respectively). Complete recovery was observed within 48 h with all chemoattractants. Normal neutrophil random migration and F-actin polymerization were found. Decreased neutrophil polarization was detected (46 +/- 6% vs 22 +/- 8% of polarized cells, before and after effort, respectively; P = 0.004). Correlation between polarization and chemotactic migration was found (r = 0.945; P = 0.001). CONCLUSIONS: The impaired chemotactic response, observed 24 h after exercise, was similar using different chemoattractants. This finding indicates a possible exercise-induced effect on a common factor at the ligand-receptor level. The abnormal cell polarization indicates skeletal dysfunction that should be further investigated and elucidated. The normal fMLP-stimulated-F-actin polymerization reflects an adequate pathway of signal transduction for the formyl peptide.

Adult↗
PubMed1992

Skeletal muscle carnitine metabolism in patients with unilateral peripheral arterial disease.

Patients with peripheral arterial disease (PAD) have abnormalities of carnitine metabolism that may contribute to their functional impairment. To test the hypothesis that muscle acylcarnitine generation (intermediates in oxidative metabolism) in patients with PAD provides a marker of the muscle dysfunction, 10 patients with unilateral PAD and 6 age-matched control subjects were studied at rest, and the patients were studied during exercise. At rest, biopsies of the gastrocnemius muscle in the patients' nonsymptomatic leg revealed a normal carnitine pool and lactate content compared with control subjects. In contrast, the patients' diseased leg had higher contents of lactate and long-chain acylcarnitines than controls. The muscle short-chain acylcarnitine content in the patients' diseased leg at rest was inversely correlated with peak exercise performance (r = -0.75, P less than 0.05). With graded treadmill exercise, only patients who exceeded their individual lactate threshold had an increase in muscle short-chain acylcarnitine content in the nonsymptomatic leg, which was identical to the muscle carnitine response in normal subjects. In the patients' diseased leg, muscle short-chain acylcarnitine content increased with exercise from 440 +/- 130 to 900 +/- 200 (SE) nmol/g (P less than 0.05). In contrast to the nonsymptomatic leg, there was no increase in muscle lactate content in the diseased leg with exercise, and the change in muscle carnitine metabolism was correlated with exercise duration (r = 0.82, P less than 0.01) and not with the lactate threshold. We conclude that energy metabolism in ischemic muscle of patients with PAD is characterized by the accumulation of acylcarnitines.(ABSTRACT TRUNCATED AT 250 WORDS)

Aged↗
PubMed2000

Complex repetitive discharges during urethral sphincter EMG: clinical correlates.

Complex repetitive discharges (CRDs) are a form of abnormal needle electromyographic (EMG) activity associated with a variety of neuromuscular disorders, including chronic denervation. Urethral CRDs have also been associated with symptoms of voiding dysfunction. We reviewed the findings of 351 consecutive urethral sphincter EMG studies to characterize the patients with CRDs in our patient population and further to characterize the peri-operative course of any patient with urethral CRDs who underwent surgery for genuine stress incontinence (GSI). Among the 351 women studied, a subgroup of 27 (8%) women demonstrated CRDs during their study. Patients with CRDs were more likely to report the symptom of strain voiding (48% of patients with CRDs, 18% of patients without CRDs; chi(2)((1)) = 17.6, P < 0.001). Patients with CRDs were also more likely to have undergone prior urethral dilation (15% of patients with CRDs versus 2% of patients without CRDs, chi(2)((1)) = 9.5, P < 0.01). Patients with CRDs were similar to patients without CRDs with respect to symptoms of incontinence and history of hysterectomy or surgery for incontinence. Ten patients who had urethral CRDs underwent surgery for their GSI with a 90% success rate. The duration of post-operative catheterization did not differ from that of our general population of patients undergoing similar procedures. Urethral CRDs appear to be a non-specific finding, and it is premature to alter the approach to patients with lower urinary tract dysfunction for this reason.

Action Potentials↗
PubMed1996

Persistent microvasculopathy in chronic eosinophilia-myalgia syndrome.

Acute eosinophilia-myalgia syndrome (EMS) due to contaminated L-tryptophan (LT) exposure is an inflammatory microangiopathy of the dermis, fascia, and muscle. Select individuals evolve from acute EMS to have persistence of myalgia, fatigue, cramps, and skin changes for years. Many develop memory dysfunction and confusion. The objective of this study is to delineate the pathology in individuals with chronic EMS. Seventeen patients with ongoing symptoms representing chronic EMS are studied by skin, fascia, and muscle biopsies four to five years after exposure to contaminated LT and initial onset of EMS. All have microvascular disease. Most have lymphocytic inflammatory infiltrates. Several have dermal sclerosis. The findings indicate that persistent microvascular disease is present in chronic EMS. The pathologic changes are similar to those of acute EMS but with notable differences. Tissue eosinophil infiltration is rare in the chronic state as compared to acute EMS. The persistence of endothelial pathology indicates continuing microvascular dysfunction.

Arterioles↗
PubMed2004

Ischemic-preconditioning does not prevent neuromuscular dysfunction after ischemia-reperfusion injury.

The primary purpose of this study was to evaluate ischemic-preconditioning (IPC) as a means of improving tolerance to ischemia-reperfusion (IR) stress on neuromuscular function. A secondary objective was to isolate the area of injury within the neuromuscular unit responsible for contractile dysfunction after IR injury. Twenty-eight male rabbits were randomly assigned to four groups (sham, IPC only, sustained ischemia only, IPC and sustained ischemia). The IPC protocol consisted of three cycles of 10 min of tourniquet-induced ischemia (125 mmHg) followed by 10 min of reperfusion. Sustained ischemia was induced by 350 mmHg external compression for 2 h. Peak tetanic tension of the tibialis anterior (TA) muscle was evaluated 48 h after the tourniquet protocol by both peroneal nerve and direct muscle stimulation, with and without pharmacologic neuromuscular junction blockade. Animals subjected to combined IPC and sustained ischemia had an equivalent loss of contractile force to those undergoing sustained ischemia alone. Two hours of tourniquet-induced ischemia resulted in marked dysfunction of the TA neuromuscular unit when evaluated by peroneal nerve stimulation (p < 0.0001). Isolation of the TA muscle from the peroneal nerve with direct muscle stimulation and neuromuscular junction blockade preserved muscle function after 3 h of ischemia. In our model, these results clearly demonstrate that IPC provides no significant protective effect from IR injury to either nerve or muscle function in our model. In addition, nerve or neuromuscular junction injury, rather than muscle damage, is identified as primarily responsible for IR-related muscle dysfunction.

Algorithms↗